Novel Potent and Selective Dopamine D4 Receptor Piperidine Antagonists as Potential Alternatives for the Treatment of Glioblastoma.

ABSTRACT: Background/Objectives: D4R antagonists have recently been suggested as potential therapeutic alternatives to the standard treatments of glioblastoma (GBM). In this study, new piperidine-based ligands, analogs of the potent and selective D4R compounds 77-LH-28-1 (7) and its 4-benzyl analog 8, were synthesized and studied to investigate the effects produced by variations in the distances between the pharmacophoric features on the D4R affinity and selectivity. Methods: All the new compounds 9-20 were evaluated for their radioligand binding affinity at D2-like receptor subtypes and the results were rationalized by docking studies and molecular dynamics (MD) simulations. The functional profiles of the most interesting derivatives were assessed at D4R Go and Gi

SUBMITTER: Matteucci F 

PROVIDER: S-EPMC12114630 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature